We reviewed the records of 25 cases of cardiac myxomas at 2 referral centers. Six patients, or 24%, had a history of malignancy. An association between prior malignancy and cardiac myxoma has not been suspected previously. The gelatinous stroma of myxomas is composed predominantly of hyaluronic acid. We propose that elevated levels of hyaluronic acid-stimulating activity occur in the circulation of some patients with an epithelial malignancy. A persistent rest of fetal-like cardiac mesenchyme cells in the area of the fossa ovalis exists in a small cadre of cancer patients. Stimulation of hyaluronic acid production and cell proliferation in the fetal cardiac rest by the cancer-derived factor may underlie the subsequent development of cardiac myxomas in such individuals.